The present invention relates to antigens from Enterococcus that are useful as vaccines, and to methods for obtaining and using such antigens.
The prevalence of Enterococcus infection is increasing steadily. Strains of Enterococcus now are responsible for 12% of all the nosocomial infections among hospitalized patients and they are the second most common organism isolated from patients with nosocomial infections. This increased prevalence of Enterococcus is due at least in part to the appearance of strains of enterococci that are resistant to antimicrobial agents and therefore difficult to treat with currently available antibiotics. The increase in antibiotic resistance among Enterococcus has increased the importance of alternative prophylactic and therapeutic approaches against enterococcal infections.
Various groups have disclosed polysaccharides isolated from Enterococcus. For example, lipoteichoic acids which contain a 1,3-linked polyglycerophosphate backbone have been isolated from “S. faecalis,” which according to current classification is E. faecalis. Position 2 is glycosylated with disaccharides or trisaccharides of glycosyl residues which may be esterified with alanyl residues, and is denoted intracellular teichoic acid because of its predominance between the cell wall and the protoplast membrane. Wicken et al., J. Gen. Microbiol. 33: 231-39 (1963).
Pazur et al., J. Biol. Chem. 246: 1793-98 (1971), have isolated two other polysaccharides from the cell wall of E. faecalis strain N. One of these polysaccharides is characterized as a diheteroglycan consisting of glucose and D-galactose, while the other polysaccharide is said to be a tetraheteroglycan of 2-acetamide-2-deoxy-galactose, galactose, rhamnose, and glucose in molar ratio of 1:1:2:4.
Bleiweis et al., J. Bacteriol. 94: 1381-87 (1967), have isolated a third polysaccharide from strain D76 of group D Streptococci. The sugar composition of this material includes glucose, glucosamine, galactosamine, rhamnose, ribitol, and phosphorus; structural information is not provided, however. It is postulated that this material may be ribitol phosphate teichoic acid with attached sugar substituents. It also has been hypothesized that glucose and N-acetyl glucosamine are the possible components of the antigenic site.
Enterococcus antigen(s) capable of eliciting protective antibodies would provide an effective means of preventing and/or treating Enterococcus infection. While the art discloses a variety of Enterococcus antigens, not every antigen is effective as a vaccine. Indeed, none of the material reported in the literature has been shown to be effective in protecting against infection by Enterococcus. In this regard, even a disclosure that an antigen is immunogenic, i.e., that it causes the production of antibodies, provides an insufficient basis for a conclusion that the antibodies are protective and that the antigen therefore is useful in a vaccine.
Finally, the art suggests that Enterococcus serologically is a very diverse genus. This serologic diversity suggested that a vaccine comprised of a practical number of active components was not feasible. Maekawa et al., Microbiol. Immunol. 36: 671-681 (1992).